Chromatography column qualification in manufacturing methods for producing anti-IL12/IL23 antibody compositions

Abstract

A method of operating a chromatography column is described for use in methods of manufacture for producing anti-IL-12 / IL-23p40 antibodies, e.g., the anti-IL-12 / IL-23p40 antibody STELARA® (ustekinumab). This method involves collecting column outlet signal and accumulated flow parameters at two or more intervals of at least one mobile phase transition front during operation of the chromatography column comprising column packing. A model gamma cumulative distribution curve is calculated based on the collected column outlet signal and accumulated flow parameters for the at least one mobile phase transition front. A height equivalent theoretical plate (HETP) value is calculated for the at least one mobile phase transition front using parameters of the model gamma cumulative distribution curve and the quality of the chromatography column packing is assessed based on the calculated HETP value.

Description

CROSS REFERENCE TO RELATED APPLICATION[0001]This application claims priority to U.S. Provisional Application No. 62 / 660,340, filed Apr. 20, 2018, which is incorporated herein by reference in its entirety.FIELD OF THE INVENTION[0002]The present invention relates to a method of chromatography column qualification in methods of manufacture for producing anti-IL-12 / IL-23p40 antibodies, e.g., the anti-IL-12 / IL-23p40 antibody STELARA® (ustekinumab), specific pharmaceutical compositions of the antibodies, and antigen binding fragments thereof.REFERENCE TO SEQUENCE LISTING SUBMITTED ELECTRONICALLY[0003]This application contains a sequence listing, which is submitted electronically via EFS-Web as an ASCII formatted sequence listing with a file name “JBI6082USNP1 Sequences”, creation date of Apr. 17, 2019 and having a size of 14 kb. The sequence listing submitted via EFS-Web is part of the specification and is herein incorporated by reference in its entirety.BACKGROUND OF THE INVENTION[0004]C...

AI Technical Summary

Benefits of technology

[0014]A primary advantage of the GDTA method is that it provides a more sensitive gauge of dispersion across the column bed than the Gaussian HETP estimation method. By using GDTA, it is no longer necessary to measure asymmetry, as the GDTA model correctly measures dispersion from the curve fit. Additionally, the use of the gamma distribution function facilitates ease of analysis of frontal transitions when compared to alternative non-gaussian methods previously reported. The use of mobile phase transitions already present in a chromatography process avoids the need for extra offline processing steps. Furthermore, in many cases, historical data allows for establishment of historical ranges of column efficiency prior to implementation. Finally, the GDTA method can be automated to ensure consistent application.

Problems solved by technology

The performance of columns must be maintained as the process is scaled-up from the bench top to manufacturing plants and throughout column lifetimes. Difficulties in column evaluation procedures, potential changes to the integrity of packed beds, and logistics can arise as the column diameter, equipment, and buffer consumption increases to scale up the process.

The primary limitation of this method is that it does not provide an accurate measure of dispersion (i.e., HETP) when the peak shape deviates from a Gaussian distribution.

The limitations of this approach result in a lack of sensitivity to changes in column performance, and often results in the repacking or conditioning of a column, while column performance is actually acceptable.

The Gaussian approaches have the same limitations in sensitivity as noted supra for the injection method and the reported non-Gaussian approaches require complex calculations.

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